Scientists have unearthed a fresh and foundational factor associated with female infertility
The alteration in a particular gene, known as Eif4enif1, has been recognised as a catalyst for an issue affecting the ovaries, hindering the likelihood of conception. Researchers at Tsinghua University in China have determined that this specific genetic modification leads to complications in egg cells, disrupting the regular release of eggs from the ovaries.
The absence of egg release, a crucial step in the ovulation process, hinders the possibility of fertilisation. More precisely, the deleterious DNA pattern impacts the functionality of mitochondria within the egg cells—the ‘powerhouse’ responsible for converting fuel into energy. This disruption in mitochondrial function plays a pivotal role in impeding the overall fertilisation process.
Infertility impacts millions of couples globally, with approximately one in six experiencing infertility. In a small percentage of these cases, the root cause lies in the failure of the ovaries to release an egg during the reproductive process.
Professor Kehkooi Kee, a key figure in the study from Tsinghua University in China, emphasised that the association between Eif4enif1 and mitochondria, uncovered through their research, represents a novel and previously unidentified link. This discovery sheds new light on the understanding of infertility, particularly in cases where egg release is compromised.
Medically termed as both primary ovarian insufficiency and premature ovarian insufficiency, issues related to the production and release of eggs occur before menopause, and the term “premature” indicates that the problem arises prior to the natural cessation of ovulation.
In a noteworthy development, the 2019 research by Chinese scientists uncovered a family with premature ovarian insufficiency, all exhibiting changes in the Eif4enif1 gene. Replicating this genetic modification in mice, the researchers examined its impact on human fertility. Comparing genetically edited mice with those whose DNA had not been altered, they observed a distinct pattern of changes in egg mitochondria.
The genetically edited mice exhibited a reduction of about 40 percent in the average number of total follicles, the sacs containing developing eggs on the ovarian surface. The average number of offspring per litter also decreased by a third, and nearly half of the fertilised eggs did not progress beyond the early developmental stages when grown in a dish.
Microscopic examination of eggs from less fertile mice revealed an abnormal clustering of mitochondria, suggesting a link between misbehaving mitochondria and infertility. The researchers hypothesize that restoring proper mitochondrial behavior could enhance fertility. The next phase involves investigating if mitochondrial defects are also present in the eggs of human patients.
The findings not only provide insights into potential treatments but also indicate the prospect of gene-editing drugs that could address the identified problem.
This groundbreaking study has been published in the journal Development.
